Transition-State Affinity as a Basis for the Design of Enzyme Inhibitors

摘要: To bring about the large rates of reaction which occur in presence enzymes, interaction between reacting substrates and enzymes must be strong intimate. The fact that form complexes with has been known since time Henri(1) Michaelis Mentent(2) exploited design inhibitors resemble substrates. Enzyme—substrate affinity is far surpassed by developed transiently during catalysis, as was recognized Paulingt(3) before much enzyme mechanisms. This enhanced can to produce more effective inhibitors, designed substrate its transformation products.(4–8) These usually designated “transition-state analogs,” (4) are bound very tightly than As mid-1975, some 60 possible examples were known, several potential transition-state analogs had also found nature.t(9,10)